One important requirement for rendering it possible to use membranes in medical procedures, such as in blood purification therapy, is that the membranes are capable of being sterilized. For reasons relating both to safety and environmental protection, and which relate to the production of by-products and toxic residues, steam sterilization or sterilization using dry heat are preferred over such sterilization procedures as the use of ethylene oxide gas, the use of plasma processes, such as with hydrogen peroxide, or the use of irradiation, such as with .gamma.-rays.
Sterilization with steam is usually effected by treating the membrane for a period of about 20 minutes with saturated steam at a temperature of about 120.degree. C. Sterilization with dry heat is usually effected for a period of about 90 minutes at 180.degree. C. (DAB 1992). Those sterilization conditions, however, result in a limitation of the number of synthetic polymers which can be used for that purpose. Thus, for example, dialysis membranes of polyacrylonitrile (U.S. Pat. No. 4,545,910), cellulose triacetate (U.S. Pat. No. 4,276,137) and partially aromatic amorphous polyamide (laid-open European Patent Application No. 305,787) cannot be sterilized with steam, because an irreversible and disadvantageous change in the pore structure occurs under these steam sterilization conditions. Hydrolysis-sensitive polymers such as poly-(carbonate block ethylene oxide) (U.S. Pat. No. 4,069,151) also cannot be sterilized with steam, since in this case the polymer would be decomposed, resulting in breaks or holes in the membrane. In addition, those membranes are impregnated with hydrophilizing agents, such as with polyvinylpyrrolidone, glycerin or polyethylene glycol (laid-open European Patent Application No. 228,072) which further increases the instability of these membrane structures by heating, as a result of the softening effect of these materials.
On the other hand, it is precisely such dialysis membranes consisting of those polymers which possess unusually good hemocompatibility in comparison with dialysis membranes of the cellulose type (see "Polyamide--the Evolution of a Synthetic Membrane for Renal Therapy", edited by S. Shaldon, K. M. Koch in Contributions to Nephrology, volume 96, Karger 1992!; E. Wegmuller, A. Montandon, "Biocompatibility of Different Hemodialysis Membranes, Activation of Complement and Leukopenia," Inte. J. Artif. Organs, 9, 85 1986!; R. M. Hakim et al., "Complement Activation and Hypersensitivity Reactions to Dialysis Membranes", New England J. Med., 311, 878 1984!; H. Schiffl, "Biocompatible Membranes in Acute Renal Failure, Prospective Casecontrolled Study," Lancet, 344, 570 1994!; and R. M. Hakim et al., "Effect of the Dialysis Membrane in the Treatment of Patients with Acute Renal Failure," New England J. Med., 311, 1338 1994!.
Furthermore, partially aromatic amorphous polyamides in particular have a particularly high endotoxin or pyrogen retention capacity. See the discussion in Lonnemann et al., "Pyrogen Retention by the Polyamide Membrane," in "Polyamide--The Evolution of a Synthetic Membrane for Renal Therapy," edited by S. Shaldon, K. M. Koch, Contributions to Nephrology, 96, 47 (1992), relating to the high level of efficiency of asymmetrical polyamide membranes with respect to endotoxin retention capacity, and which attributes crucial significance to the interaction of the pyrogenic bacterial substances with the hydrophobic domains of the membrane, which are formed by polyamides.
Laid-open European Patent Application No. 604,882 describes a semipermeable membrane comprising sulphonated aromatic polyetherketone and fully aromatic polyamide, possibly with the addition of polyvinylpyrrolidone. These two polymers are thermally stable under the conditions of steam sterilization, so that it is not surprising that such a membrane is sterilizable with steam.
It is therefore an object of the present invention to provide a membrane which can be sterilized with heat, and in particular with steam, while also using a polymer, such as a polyamide or polyvinylpyrrolidone, which is unstable under the usual conditions of sterilization with steam or dry heat, that is to say with saturated steam and at a temperature of about 120.degree. C.